New score identifies patients at risk for progressive nonalcoholic steatohepatitis

Last Updated: 2020-02-18

By Will Boggs MD

NEW YORK (Reuters Health) - A newly developed score can accurately identify patients at risk for progressive nonalcoholic steatohepatitis (NASH), thereby sparing patients unlikely to have significant disease an unnecessary biopsy, researchers report.

Most patients with nonalcoholic fatty-liver disease (NAFLD) do not progress to advanced fibrosis or cirrhosis, and identifying those at greatest risk of clinical progression who might benefit from treatment with new pharmacotherapies remains a challenge.

Dr. Philip N. Newsome of the University of Birmingham, in the UK, and colleagues used data from an earlier trial to develop an algorithm for identifying NASH, significant liver fibrosis, and an elevated NAFLD activity score among people with suspected NAFLD.

The FibroScan-AST (FAST) score combining liver-stiffness measurement (LSM) by elastography, controlled attenuation parameter (CAP) and aspartate aminotransferase (AST) proved best for predicting progression, the researchers report in The Lancet Gastroenterology and Hepatology.

With cutoffs of at least 90% sensitivity (a FAST score of 0.35) and at least 90% specificity (a FAST score of 0.67), the positive predictive value (PPV) was 83%, and the negative predictive value (NPV) was 85% in the derivation cohort, with 39% of patients in the gray zone between the two cutoffs.

In the validation cohort, a FAST score of 0.35 or less ruled out NASH progression in 51% of individuals, and a FAST score of 0.67 or higher ruled in NASH progression in 19% of individuals, leaving only 30% of individuals in the gray zone where biopsy might be required to make a final adjudication.

The FAST score showed significantly better discrimination than either the NAFLD fibrosis score or the fibrosis-4 (FIB-4) index for identifying patients who would meet the historical target used to identify patients for clinical trials of NASH treatment.

"We believe the FAST score will allow for the more efficient identification of an at-risk group of patients with progressive NASH that merit consideration for further treatment," the authors conclude.

Dr. Ian A. Rowe of the University of Leeds, in the UK, who wrote a linked editorial, told Reuters Health by email, "The FAST score might be useful for the identification of patients for clinical trials in NASH where we know that patients being considered are often ineligible to participate. This ineligibility is most often related to NASH not being severe enough to warrant treatment."

"There are questions about how well the FAST score can identify patients above FibroScan-based evaluation of fibrosis," he said. "As I say in the editorial, many patients who would not be biopsied when the FAST score is used would not have been biopsied based on fibrosis alone."

"In practice, there are too many uncertainties around the efficacy of treatment to understand how the FAST score might be used," Dr. Rowe said. "If treatment was highly efficacious, then one might accept high rates of biopsy because the risk-benefit balance would be in the patient's favor. If treatments were less effective, then the score might be more useful, as one would want to look for reasons not to biopsy."

Dr. Hannes Hagstroem of Karolinska University Hospital in Stockholm, whose research has shown that fibrosis stage predicts mortality and progression in biopsy-proven NAFLD, told Reuters Health by email, "A simple algorithm can be used to improve screen failure rate in clinical trials for NAFLD, and possibly in the future help in determining which patients could be eligible for treatments, once approved."

"The limitation of the FAST score, as I see it, is that it needs a specific hardware (FibroScan) to use, and thereby would be difficult to use in primary-care settings, as this is still relatively expensive," said Dr. Hagstroem, who was not involved in the new work. "Also, the prevalence of advanced stages of fibrosis was relatively high, higher than in primary-care populations, so it is uncertain if the performance of the new test would be as good in populations with lower prevalences of fibrosis."

Dr. Arun J. Sanyal of Virginia Commonwealth University, in Richmond, who studies NAFLD but was not involved in the study either, told Reuters Health by email the FAST score "adds to precision of FibroScan to identify clinically significant fibrosis but does not solve other major needs for noninvasive tests for NASH; more work is needed."

Dr. Newsome did not respond to a request for comments.

Echosens, which makes the FibroScan device, funded the study and employed several of the authors.

SOURCE: https://bit.ly/3bSFg7J and https://bit.ly/2HxT4Gq Lancet Gastroenterology and Hepatology, online February 3, 2020.